1. Field of the Invention
This invention relates to bioprosthetic transcatheter valve and implant material, processes for preparing bioprosthetic transcatheter valve and implant material from animal tissue, and methods of use thereof. Specifically, the invention relates to the preparation of animal tissue, in which the tissue is cleaned, chemically cross-linked using both vaporized and liquid cross-linking agents, and compressed, resulting in an improved bioprosthetic or implantable material that is substantially non-antigenic, non-thrombogenic, resistant to calcification, durable, and thin enough to be used in applications requiring extremely small valves or implants.
2. Background of the Invention
The use of prepared heterogenous graft material for human surgical implantation is well known. More specifically, the use of treated animal tissue as human tissue grafts, replacement valves, and similar implantation surgical procedures is well known. However, problems of immunogenicity, thrombogenicity, calcification, material strength, and size have not been adequately addressed in the prior art.
Prior to the present invention, animal tissue specimens for surgical use were prepared by first harvesting the selected tissue from beef cattle or other meat supplying animals at the slaughter house. The harvested tissues were then transported to a laboratory where the material was cleaned by mechanically stripping away fat tissue and other undesired components from the harvested specimen material. Next, the cleaned tissue specimen was subjected to a “wet” cross-linking operation in which it is soaked for a predetermined time in a glutaraldehyde solution and finally was dehydrated in an alcohol solution. Subsequently, the sample was thoroughly rinsed to remove traces of the ethyl alcohol and glutaraldehyde and then was packaged in a vial containing a one percent propylene oxide solution as a sterilant.
While the use of cattle or other meat supplying animals ensures an adequate supply of tissue for processing, a combination of (i) the lower natural collagen levels and higher non-collagenous protein levels in the tissue of older animals, (ii) the lack of a processing step to effectively remove non-collagenous proteins, and (iii) the limitations of “wet” cross-linking, when used alone, to bond glutaraldehyde with collagen molecules, results in a product that still exhibits traits of antigenicity, thrombogenicity and calcification that can result in post-surgical complications, as well as limited endothelialization properties.
More specifically, the use of glutaraldehyde alone in chemical cross-linking of tissue results in a tissue sample wherein the release of glutaraldehyde after implantation of the sample results in an increased risk of inflammation in and around the implanted tissue.
For example, U.S. Pat. No. 6,468,313 to Bio-Vascular, Inc. discloses an implant material in the form of a natural animal tissue cross-linked into a pre-formed shape, the tissue being adapted to substantially retain its shape when implanted into a body.
In another example, U.S. Pat. No. 5,507,810 to Osteotech, Inc. discloses fibrous connective tissue for surgical implantation is made substantially antigen-free by contact with one or more extraction agents.
In another example, U.S. Pat. No. 4,681,588 to Ketharanathan discloses material for use in a biological environment is produced by subjecting a sheet of parietal pleura to glutaraldehyde tanning.
In another example, U.S. Pat. No. 4,399,123 to Oliver discloses a fibrous tissue preparation suitable for homo or heterotransplantation obtained by treating mammalian fibrous tissue with a proteolytic enzyme followed, if desired, by further treatment with a carbohydrate splitting enzyme.
However, known procedures for treating animal tissue typically result in tissue thickness too large for surgical use in applications requiring a smaller valve or implant. Tissue samples of this thickness can limit the use of smaller gauge catheters in delivering the tissue sample to the area of the human body in which surgery is to be performed, or limit the types of patients that may be treated to large patients only.
For example, bovine pericardial tissue used in the products Duraguard®, Peri-Guard®, and Vascu-Guard®, all products currently used in surgical procedures, are marketed as being harvested generally from cattle less than 30 months old. However, pericardial tissue from older animals is thicker than younger animals, and thus limits the thinness that can be achieved. Other patents and publications that are directed to the surgical use of harvested, biocompatible animal tissues may disclose thin tissues, however, these tissues are used only as biocompatible “jackets” or sleeves for implantable stents. Accordingly, these tissues do not have the biomechanical, e.g. strength and durability, necessary for the construction of bioprosthetic transcatheter valves, or implants. For example, U.S. Pat. No. 5,554,185 to Block discloses an inflatable prosthetic cardiovascular valve which is constructed so as to be initially deployable in a deflated “collapsed” configuration wherein the valve may be passed through the lumen of a cardiovascular catheter and subsequently inflated to an “operative” configuration so as to perform its intended valving function at its intended site of implantation within the cardiovascular system. In another example, U.S. Pat. No. 7,108,717 to Design & Performance-Cyprus Limited discloses a covered stent assembly comprising a tubular, expandable stent having a metallic framework covered with a cylinder of biocompatible, non-thrombogenic expandable material, such as heterologous tissue. In another example, U.S. Pat. No. 6,440,164 to Scimed Life Systems, Inc. discloses a prosthetic valve for implantation within a fluid conducting lumen within a body includes an elongate generally cylindrical radially collapsible valve body scaffold defining a fluid passageway therethrough for retentive positioning within the lumen. However, these patents describe necessarily elastic materials that are used for covering expandable wire-mesh stents.
Methods do currently exist for production of synthetic bioprosthetic materials in the form of an acellular collagen-based tissue matrix. However, the product suffers from a strength deficiency, is subject to tearing and is not ideal for suture retention. For example, U.S. Pat. No. 5,336,616 to LifeCell Corporation discloses a method for processing and preserving an acellular collagen-based tissue matrix for transplantation. However, to date, the molecular reasons why naturally matured collagen is superior to synthetic have not been fully elucidated.
Accordingly, procedures and devices which address these and other concerns are needed in the field.